X-129920506-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006649.4(UTP14A):​c.802T>A​(p.Phe268Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

UTP14A
NM_006649.4 missense

Scores

2
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65
Variant links:
Genes affected
UTP14A (HGNC:10665): (UTP14A small subunit processome component) This gene encodes a member of the uridine triphosphate 14 family. As an essential component of a large ribonucleoprotein complex bound to the U3 small nucleolar RNA, the encoded protein is involved in ribosome biogenesis and 18S rRNA synthesis. An autosomal retrotransposed copy of this X-linked gene exists on chromosome 13. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UTP14ANM_006649.4 linkuse as main transcriptc.802T>A p.Phe268Ile missense_variant 9/15 ENST00000394422.8 NP_006640.2 Q9BVJ6-1
UTP14ANM_001166221.2 linkuse as main transcriptc.646T>A p.Phe216Ile missense_variant 8/14 NP_001159693.1 Q9BVJ6-3
UTP14AXM_047441790.1 linkuse as main transcriptc.370T>A p.Phe124Ile missense_variant 5/11 XP_047297746.1
LOC105373335NR_188631.1 linkuse as main transcriptn.218+9252A>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UTP14AENST00000394422.8 linkuse as main transcriptc.802T>A p.Phe268Ile missense_variant 9/151 NM_006649.4 ENSP00000377944.3 Q9BVJ6-1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
22
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 26, 2022The c.802T>A (p.F268I) alteration is located in exon 9 (coding exon 9) of the UTP14A gene. This alteration results from a T to A substitution at nucleotide position 802, causing the phenylalanine (F) at amino acid position 268 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.47
BayesDel_addAF
Benign
-0.019
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.071
.;T;T
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Uncertain
0.22
D
MetaRNN
Uncertain
0.55
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.0
.;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.023
D;D;D
Sift4G
Benign
0.36
T;T;T
Polyphen
0.76
.;P;.
Vest4
0.55
MutPred
0.61
.;Loss of helix (P = 0.0558);.;
MVP
0.51
MPC
0.88
ClinPred
0.99
D
GERP RS
6.2
Varity_R
0.71
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1383583388; hg19: chrX-129054482; API